The Study of Prevalence and Pattern of Thyroid Disorder in Pregnant Women: A Prospective Study

Background The most frequent thyroid disorder in pregnancy is maternal hypothyroidism. The geographical variation in the prevalence of hypothyroidism during pregnancy is very wide and ranges from 2.5% to 11%. The prevalence of hypothyroidism is more in Asian countries as compared to western countries. Thus, this study was conducted to find out the prevalence of thyroid disorder in pregnancy at our center. Methods The present study was conducted in the Department of Physiology in collaboration with the Department of Obstetrics & Gynecology, Index Medical College, Hospital and Research Center, Indore, MP, India over a period of one and a half years from October 2018 to March 2020. It was a cross-sectional study including 865 pregnant women. The patients' demographic profile was noted in all cases. A detailed history and thorough examination were done in all cases. Serum thyroid-stimulating hormone (TSH), Free T3, and Free T4 (FT3 and FT4) were done along with routine blood investigations as per The Federation of Obstetric and Gynaecological Societies of India-Indian College of Obstetricians and Gynaecologists (FOGSI-ICOG) good clinical practice recommendation. Results In this study, the prevalence of thyroid dysfunction was 10.4%. Of these 90 patients with thyroid dysfunction, subclinical and overt hypothyroidism was found in 5.50% and 0.92%, respectively, whereas subclinical and overt hyperthyroidism was observed in 3.12% and 0.81% pregnant females, respectively. A significant association was found between thyroid dysfunction and maternal age, BMI, parity, and education. Conclusions The prevalence of thyroid dysfunction was 10.4% in this study. Hypothyroidism was more common than hyperthyroidism and subclinical thyroid disorders were more common than overt thyroid disorders in pregnancy. Therefore, we should include thyroid function tests with other routine investigations during pregnancy to detect thyroid dysfunction.


Introduction
The most frequent thyroid disorder in pregnancy is maternal hypothyroidism. The geographical variation in the prevalence of hypothyroidism during pregnancy is very wide and ranges from 2.5% to 11% [1]. The prevalence of hypothyroidism is more in Asian countries as compared to western countries. Untreated or inadequately treated and subclinical hypothyroidism all can increase the risk of miscarriage, preeclampsia, anemia, fetal growth restriction, placental abruption, perinatal and neonatal morbidity and mortality, preterm delivery, small head circumference, and low birth weight impaired neuropsychological development [2]. Hypothyroidism consists of two clinical forms: subclinical and overt hypothyroidism. The subclinical hypothyroidism is characterized by an elevated serum thyroid-stimulating hormone (TSH) with normal free thyroxine (FT4) and is observed in 3%-5% of women in pregnancy. Overt hypothyroidism is characterized by an elevated serum TSH and subnormal FT4 is observed in 0.3%-0.5% of women in pregnancy [3,4].
The occurrence of hyperthyroidism is less during pregnancy with the prevalence being 0.1%-0.4%. Overt hyperthyroidism is seen in nearly 2% of pregnancy characterized by a reduced TSH and an increased FT3/FT4 while subclinical hyperthyroidism is seen in 1.7% of pregnancy and is characterized by a suppressed serum TSH and normal FT4 [5]. Physiological changes during pregnancy may mimic hyperthyroidism like fatigue, anxiety, increase in basal metabolism, heart rate, palpitations, heat intolerance, warm and wet skin, hand tremors, and systolic murmur, which causes difficulty in diagnosis [6,7]. Pregnant women suffering from hyperthyroidism have more severe tachycardia and thyromegaly, along with exophthalmia, and lack of weight gain despite having adequate food [1]. Thyroid dysfunction is usually overlooked and ignored in pregnant women because of the non-specific and hypermetabolic state of pregnancy [8]. Thus, this study was conducted to find out the prevalence of thyroid disorders in pregnancy at our center.

Materials And Methods
The present study was conducted in the Department of Physiology in collaboration with the Department of Obstetrics and Gynecology, Index Medical College, Hospital and Research Center, Indore, MP, India over a period of one and a half years from October 2018 to March 2020. It was a cross-sectional study including 865 pregnant women attending clinics in the study period. All antenatal women in their first-trimester pregnancy were included after taking consent except patients with known thyroid disorders, multiple gestations, hypertension, diabetes mellitus, and other medical disorders. The patient's demographic profile was noted in all cases. After a detailed history and thorough examination, screening for thyroid disorder was done with serum TSH assay along with other routine investigations of pregnancy as per The Federation of Obstetric and Gynaecological Societies of India-Indian College of Obstetricians and Gynaecologists (FOGSI-ICOG) good clinical practice recommendation. Those with abnormal TSH were subjected to FT4, FT3, and anti-thyroid peroxidase antibody assay. Women diagnosed with abnormal thyroid functions were referred to the endocrinology department for the treatment of thyroid dysfunction. Hypothyroid patients (subclinical and overt variety) were treated with levothyroxine while hyperthyroidism was treated with propylthiouracil. Repeat thyroid profiles were done at 4-6 weeks intervals and treatment was adjusted to keep the serum TSH levels within normal limits.
The reference range used in the study was based on the guidelines of the American Thyroid Association (ATA) 2017 [9]. According to which normal levels of TSH during 1st, 2nd, and 3rd trimester of pregnancy are 0.1-2.5 mIU/L, 0.2-3.0 mIU/L, and 0.3-3.0 mIU/L, respectively, and normal levels of FT4 and FT3 during pregnancy are 0.7-1.8 pg/mL and 1.7-4.2 pg/mL, respectively. Depending on the normal values, patients were classified into subclinical hypothyroidism (high serum TSH with normal FT4, FT3 level), overt hypothyroidism (high serum TSH with FT4, FT3 less than normal), subclinical hyperthyroidism (low serum TSH with normal FT3, FT4), and overt hyperthyroidism (low serum TSH with FT4 and FT3 more than normal range). The data were analyzed using the IBM SPSS version 23 (Armonk, NY). Discrete (categorical) groups, compared by Chi-squared test (χ2) to correlate demographic distribution in groups. P-value less than 0.05 (p < 0.05) was considered statistically significant.

Results
In our study, 90 patients out of 865 pregnant women have a thyroid disorder. The prevalence of thyroid dysfunction in our study was 10.40% in which the prevalence of hypothyroidism and hyperthyroidism was 6.47% and 3.93%, respectively. Of these 90 patients with thyroid dysfunction, hypothyroidism was diagnosed in 56 (62.2%) whereas hyperthyroidism was in 34 (37.8%) patients. Subclinical hypothyroidism and overt hypothyroidism were observed in 48 (53.3%) and 8 (8.9%) patients, respectively, while subclinical and overt hyperthyroidism was observed in 27 (30%) and 7 (7.78%) women, respectively.
Patients with subclinical hypothyroidism, overt hypothyroidism, overt hyperthyroidism were more common in the age group of more than 30 years while patients with subclinical hyperthyroidism were more common in the age group of less than 30 years and significant distribution was observed between thyroid disorders with age ( Table 1).  There is a causal relationship between BMI and thyroid dysfunction. All types of thyroid dysfunction were more common in overweight and obese patients, and thyroid disorder with BMI distribution was observed significantly (  The majority of the subclinical and overt hypothyroidism patients were multipara, while subclinical and overt hyperthyroidism was more common in the primipara women group and association was significant ( Table 3).  Maximum cases of subclinical hypothyroidism and overt hyperthyroidism patients were found in the educated group (Primary to Graduate) while subclinical hyperthyroidism and overt hypothyroidism patients were found in the Illiterate group and the distribution of thyroid disorder with education was significant ( Table 4).

Discussion
In our study, the prevalence of thyroid dysfunction was found to be 10.40% and this was comparable by various other Indian and foreign studies ( Table 5) [4,10,[11][12][13].

Studies Prevalence
Mulik J et al. [10] 12.15% Sahu MT et al. [11] 12.7% Azenabor A et al. [12] 11.1% Singh A and Reddy MJ [4] 8.25% Chunchaiah S et al. [13] 11.25% Present study 10.40%  In this study, the prevalence of subclinical hypothyroidism and overt hypothyroidism was 5.50% and 0.92% respectively, while subclinical hyperthyroidism and overt hyperthyroidism were 3.12% and 0.81% respectively. Thus hypothyroidism was found more common in pregnant women than hyperthyroidism in our study, which was similar to the studies conducted by Sahu   The distribution of various types of thyroid dysfunction with respect to age was found to be statistically significant (p-value < 0.001) which was similar to a study done by Ajmani SN et al. who reported an increased occurrence of thyroid dysfunction with advanced maternal age [18]. Abd Elwahid Suliman AA et al. also reported that older women were more likely to have hypothyroidism than younger [19].
In our study, we observed a statistically significant distribution (P-value < 0.001) of BMI with the women suffering from thyroid dysfunction which was contrary to Pillai NS and Bennett J study in which they observed an increased risk of hypothyroidism in pregnancy as the BMI increases and the p-value was statistically significant (p = 0.015) [24]. A study by Abdulslam K et al. and Ajmani SN et al. also showed an increase in the incidence of thyroid dysfunction with increasing BMI [14,18]. This shows that BMI plays a significant role in the prevalence of thyroid dysfunction, as the BMI increases, the prevalence of thyroid dysfunction also increases significantly.
In this study, the majority of the subclinical and overt hypothyroidism patients was found in multiple parity women while subclinical and overt hyperthyroidism was more common in single parity women and association was statistically significant (p < 0.05) which was similar to Abd Elwahid Suliman AA et al. study in which they reported a significant association between parity and overt hypothyroidism [19]. While the study of Prasad DR et al. showed no statistically significant difference (p > 0.05) between parity and hypothyroidism and Nirmala C et al. also found that maternal outcome of hypothyroidism in pregnancy of South Indian females have no statistical difference with respect to parity in different groups [25,26].
In our study, the majority of the subclinical hypothyroidism and overt hyperthyroidism patients was found in the Educated group (Primary to Graduate) while subclinical hyperthyroidism and overt hypothyroidism patients were found in the Illiterate group and the association was significant (p < 0.05) which was similar to the study of Abd Elwahid Suliman AA et al. [19]. However, in the studies of Behrooz HG et al. and Manju VK and Sathiamma PK, they reported an insignificant association (p > 0.05) between educational status and thyroid disorders [27,28].

Conclusions
In our study, the prevalence of thyroid dysfunction in pregnant women was found to be 10.40% and the prevalence of subclinical hypothyroidism and overt hypothyroidism was found to be 5.50% and 0.92%, respectively, while subclinical hyperthyroidism and overt hyperthyroidism was 3.12% and 0.81%, respectively. In our study, we conclude that subclinical hypothyroidism is more common than hyperthyroidism in pregnant women. Therefore, we should include thyroid function tests with other routine investigations during pregnancy to detect thyroid dysfunction.